Compounds, compositions and methods for binding bio-affecting substances to surface membranes of bio-particles

Abstract

Compounds, compositions, their methods of preparation and use in binding bio-affecting substances to the surface membrane of bioparticles, such as enkaryotic cells, without producing appreciable detrimental effect on morphology or physiological function of cells.

What is claimed is: 
     
       1. A composition for binding a diagnostic agent to the surface membrane of a viable bioparticle capable of physiological function, said composition comprising a compound of the formula, R-B-R 1 , wherein B represents a diagnostic agent selected from the group consisting of cyanine, acridine, pyridine, anthraquinone, coumarin, quinoline, xanthene, phenoxazine, phenothiazine and hexatriene dyes and and R and R 1  represent substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkaryl or aralkyl, the hydrocarbon chains of which are linear or branched, said substituents being unsubstituted or substituted with one or more non-polar functional groups, one of R or R 1  having at least 12 linear carbon atoms and the sum of the linear carbon atoms in R and R 1  totaling at least 23, said compound being sufficiently non-polar as to have a surface membrane retention coefficient of at least about 90 during a 24 hour period in saline containing up to 10 percent serum and the percent change in said coefficient during said period being less than 10 percent, and the compound solubility determination deviation of said compound being no more than 20 percent during two hours when dissolved in said binding medium; and a compatible binding medium in which said compound is dissolved, said medium being iso-osmotic for the bioparticle to which the compound is to be bound. 
     
     
       2. A composition as claimed in claim 1, wherein said medium has iso-osmotic properties at between 260 mOs and 340 mOs and is isotonic for the bioparticle to which the compound is to be bound. 
     
     
       3. A composition as claimed in claim 1, wherein said medium is selected from the group of a sugar, a sugar-alcohol, an amino acid, a Good's buffer or a combination thereof. 
     
     
       4. A composition for binding a diagnostic agent to the surface membrane of a viable bioparticle capable of physiological function, said composition comprising: a) a compound having the formula: ##STR23## wherein R and R 1  are different and represent substituents independently selected from the group of hydrogen, alkyl, alkenyl, alkynyl, alkaryl or aralkyl, the hydrocarbon chains of which having from 1 to 30 carbon atoms, and being linear or branched, said substituents being unsubstituted or substituted with one or more non-polar functional groups, one of R or R 1  having at least 12 linear carbon atoms, and the sum of the linear carbon atoms in R and R 1  being at least 23; X and X 1  may be the same or different and represent O, S, C(CH 3 ) 2  or Se;   Y represents a linking group selected from --CH═, --CH═CH--CH═, --CH═CH--CH═CH--CH═, or --CH═CH--CH═CH--CH═CH--CH═;   Z represents a substituent selected from the group H, alkyl, OH, NH 2 , COOH, CONH 2 , SO 3  H, SO 3  NH 2 , CONH--alkyl, CON(alkyl) 2 , NH-acyl, O-alkyl, NH-alkyl, N(alkyl) 2 , SH, S-alkyl, NO 2  or halogen, the alkyl groups comprising said Z substituents having from 1 to 3 carbon atoms;   and A represents a biologically compatible anion; and     b) a compatible binding medium in which said compound is dissolved, said medium being iso-osmotic for the bioparticle to which the compound is to be bound.   
     
     
       5. A composition for binding a diagnostic agent to the surface membrane of a viable bioparticle capable of physiological function, said composition comprising: a) a compound having the formula: ##STR24## wherein R and R 1  are different and represent alkyl substituents, having from 1 to 30 carbon atoms, and being linear or branched, unsubstituted or substituted with halogen, one of R or R 1  having at least 12 linear carbon atoms and the sum of the linear atoms in R and R 1  being at least 23; Z represents a substituent selected from the group H, or lower alkyl having from 1 to 3 carbon atoms; and   A represents a biologically compatible anion; and a compatible binding medium in which said compound is dissolved, said medium being iso-osmotic for the bioparticle to which the compound is to be bound.     
     
     
       6. A composition as claimed in claim 5, wherein said compound is 3-n-Pentyl-3'-n-octadecyloxacarbocyanine Iodide. 
     
     
       7. A composition as claimed in claim 5, wherein said compound is 3-n-Octyl-3'-n-octadecyloxacarbocyanine Iodide. 
     
     
       8. A composition as claimed in claim 5, wherein said compound is 3-n-Propyl-3'-n-eicosanyloxacarbocyanine Iodide. 
     
     
       9. A composition as claimed in claim 5, wherein said compound is 3-n-Propyl-3'-n-docosanyloxacarbocyanine Iodide. 
     
     
       10. A composition for binding a diagnostic agent to the surface membrane of a viable bioparticle capable of physiological function, said composition comprising: a) a compound of the formula: ##STR25## wherein R represents a substituent selected from the group of alkyl, alkenyl, alkynyl, alkaryl or aralkyl, the hydrocarbon chain of which is linear or branched, said substituent being unsubstituted or substituted with one or more non-polar functional groups, and having at least 23 linear carbon atoms; Z represents a substituent selected from the group H, alkyl, OH, NH 2 , COOH, CONH 2 , SO 3  H, SO 2  NH 2 , CONH-alkyl, CON-(alkyl) 2 , NH-acyl, O-alkyl, NH-alkyl, N(alkyl) 2 , SH, S-alkyl, NO 2  or halogen, the alkyl groups comprising said Z substituents having from 1 to 3 carbon atoms; and   A represents a biologically compatible anion; and     b) a compatible binding medium in which said compound is dissolved, said medium being iso-osmotic for the bioparticle to which the compound is to be bound.   
     
     
       11. A composition as claimed in claim 10, wherein said compound is 3,6-bis (dimethylamino)-10-n-hexacosanyl acridinium iodide. 
     
     
       12. A composition as claimed in claim 1, wherein said hydrocarbon substituent comprises a radioisotope. 
     
     
       13. A composition as claimed in claim 12, wherein said radioisotope is selected from the group of radioactive hydrogen, carbon, nitrogen, phosphorus, fluorine, chlorine, iodine, sulphur and selenium.